Cmv1-Independent Antiviral Role of NK Cells Revealed in Murine Cytomegalovirus-Infected New Zealand White Mice

Abstract

Ly49H+ NK cells play a critical role in innate antiviral immune responses to murine CMV (MCMV). Ly49Hb6 recognition of MCMV-encoded m157 on infected cells activates natural killing required for host resistance. We show that mAb 3D10 (anti-Ly49H) recognizes comparable subsets of NK cells from New Zealand White (NZW), New Zealand Black (NZB), and C57BL/6 spleens. However, virus levels in the spleens of MCMV-infected NZW and NZB mice differed greatly. We found that MCMV replication in infected NZW spleens was limited through NK cells. Alternately, NZB mice were profoundly susceptible to MCMV infection. Although 3D10 mAb injections given before infection interfere with Cmv1-type resistance in C57BL/6 mice, similar mAb injections did not affect NZW resistance, likely because NZW NK cell receptors did not bind MCMV-encoded m157. Instead, anti-MCMV host defenses in hybrid NZ offspring were associated with multiple chromosome locations including several putative quantitative trait loci that did not overlap with H-2 or NK gene complex loci. This study revealed a novel pathway used by NK cells to defend against MCMV infection. Thus, the importance of Ly49H in MCMV infection may be shaped by other additional background genes.

Natural Killer Cells Regulate Murine Cytomegalovirus-Induced Sialadenitis and Salivary Gland Disease

“…In contrast, a disproportionate increase in the viral load was observed for spleens of NZM mice (Fig. 1C), consistent with the lack of highly efficient NK-mediated MCMV resistance in NZM2328 mice (43). Altogether, these data demonstrate that SG function is very sensitive to viral infection in lupusprone and non-lupus-prone strains within days after MCMV infection.…”

Deficient Major Histocompatibility Complex-Linked Innate Murine Cytomegalovirus Immunity in MA/My.L-H2bMice and Viral Downregulation of H-2kClass I Proteins

“…Experimental mice (8 to 12 weeks of age) were intraperitoneally infected with MCMV (1 ϫ 10 5 PFU). On d 3.5 postinfection (84 to 90 h), spleen and liver virus levels were quantified using quantitative real-time PCR (QPCR) as described previously (29,40). All sample measurements were performed in triplicate.…”

“…MCMV (Smith strain, ATCC VR 194) salivary gland stock virus was prepared after serial passage in BALB/c as described previously (29). Experimental mice (8 to 12 weeks of age) were intraperitoneally infected with MCMV (1 ϫ 10 5 PFU).…”

A flow cytometry-based method for detecting antibody responses to murine cytomegalovirus infection

“…Work by Jonic et al using B-cell deficient mice clearly supports the hypothesis that humoral responses are dispensable during primary MCMV infection (Jonjic et al, 1994), but B-cell knockout mice used in these studies had a C57BL/6 background. C57BL/ 6 mice have well described alternative pathways to control MCMV Rodriguez et al, 2004;Scalzo et al, 1990), and therefore extrapolating these results to BALB/c mice might be inappropriate. It is therefore possible that antibody responses in BALB/ c mice are more important in viral control than in C57BL/6 mice.…”